Recently, we found that Aβ mediates the association between ApoE4 and faster tau accumulation in regions that are vulnerable for early tau aggregation (Steward et al, 2023), thus, ApoE4 might only drive Aβ-related p-tau increases in early AD disease stages, while in later disease, the effects of ApoE4 on p-tau might be independent of Aβ fibrillization. This evidence concerns the gene MAPT and Alzheimer disease.